We are studying the structure and function of malarial proteins inserted into the membrane of erythrocytes infected with mature asexual malaria parasites and molecules on the endothelial cells involved in cytoadherence. The very large cell surface protein (Mr300,000) on P. falciparum infected erythrocytes from Aotus monkeys has now been shown to be present on K+ infected cells but not K- (i.e. non-cytoadherent) cells. We have also identified this molecule on infected cells directly from Gambian malaria patients. Current experiments aim to obtain the sequence of this protein in order to more precisely study its role in cytoadherence. P. falciparum infected erythrocytes from Gambian patients have been shown by serological tests with antibodies from the same patients to express an extreme degree of antigenic diversity. Ten samples from children expressed ten different phenotypes of the infected cell surface antigen(s). Importantly, sera from Gambian adults contain antibodies which recognize an antigenically conserved epitope expressed by the malaria parasite on infected erythrocytes from all patients. Thrombospondin, a protein generally associated with agglutination of activated platelets, has been identified as a potential lignad for recognition by P. falciparum-infected cells in the endothelial cell cytoadherence phenomenon. This protein is synthesized by endothelial cells and, as a pure protein coated on plastic or glass, will specifically bind K+ P. falciparum-infected cells but not K- cells. We are attempting to identify the nature of the surface component on infected erythrocytes which binds to thrombospondin.